Cells that suffer DNA damage temporarily stop dividing until the damage has been repaired or removed. If DNA damage cannot be repaired, cells enter a state of cellular senescence to avoid progressing to a tumorigenic state. Cellular senescence, however, has also been causally linked with aging.

In an effort to understand possible sources of persistent DNA damage, Fumagalli et al. show that our genomes are differentially susceptible to being repaired. Although senescent cells are capable of repairing damage, they cannot do so when the damage is localized near the ends of our linear chromosomes. Chromosomes are capped by specialized structures known as telomeres, which consist of multiple DNA repeats bound by a protein complex (shelterin) that protects the ends from inadvertently being recognized as DNA damage. Indeed, the presence of telomeric DNA repeats or one of the shelterin proteins (TRF2) near DNA damage interferes with the normal repair process, which results in persistent DNA damage signaling. Persistent damage also accumulates at telomeres (which themselves have not become critically shortened) in aging baboons, linking DNA damage at repair-resistant telomeres with aging.